tolerance and pharmacokinetic study of chlorogenic acid to advanced glioblastoma

Conditions: Glioblastoma

Summary: the purpose of this study: determining the maximum tolerated dose (mtd), dose-limiting toxicity (dlt), pharmacokinetics characteristic, and dosage regimen of phase ii/iii of chlorogenic acid for injection in the advanced glioblastoma patients ;

1. investigate the tolerance of chlorogenic acid for injection in human body, determine the maximum tolerated dose (mtd) and dose-limiting toxicity (dlt) of chlorogenic acid for injection in the advanced glioblastoma patients ; 2. determine the human pharmacokinetics characteristic of chlorogenic acid for injection; 3. preliminary observation the effectiveness and effective dose; 4. provide the basis for the dosage regimen of phase ii/iii.

Eligibility criteria:
inclusion criteria: 1. patients with pathologic or/and fnac confirmation of advanced glioblastoma(who,iii-iv grade) but without effective treatment or with treatment failure; 2. between 18 and 65 years of age, kps≥40; 3. according to rano(2010), the parents will be eligible if one of the following conditions apply: steroid dose increased or stable,the enhanced tumor lesion increased more than 25%; the unenhanced tumor lesion increased because of the progressive tumor,even if the lesion was unmeasurable. 4. life expectancy of at least three (3) months at the enrollment; 5. patients who have sufficient baseline organ function and whose laboratory data can meet the following criteria at the enrollment: 1)plt count≥100×10\~9/l, 2)wlb count≥4.0×10\~9/l and ≤12×10\~9/l, 3)neutrophil granulocyte count≥2.0×10\~9/l, 4)hgb count≥90g/l, 5)total bilirubin \<=1.5 times of uln, 6)alt/ast ≤2.5 times of uln, 7)scr≤1.5 times of uln, 8)normal ecg with lvef (≥50%) measured by echocardiography; 6.female patients with negative pregnant test, and male/female patients of reproductive age without pregnancy planning in the next 12 months; 7.volunteered for the phase 1 trial and sign the informed consent without protest; exclusion criteria: 1. patients who have received large area radiotherapy （\>30% marrow capacity）; 2. without pathologic or/and fnac confirmation of advanced glioblastoma; 3. patients who has primary immunodeficiency diseases； 4. patients who suffer from other serious complication, such as uncontrollable infection, myocardial infarction within the past 6 months at the enrollment , uncontrollable hypertension ,thromboembolism and etc.; 5. patients who have received the therapy of chemotherapy or radical radiotherapy within 4 weeks before enrollment; 6. patients who have used nitrosoureas drug or mitomycin within 6 weeks or tyrosine kinase inhibitor within 2 weeks before enrollment; 7. patients who have received therapy of major surgery within 4 weeks or biopsy surgery within 2 weeks before enrollment; 8. patients who experience grade 2 or more than grade 2 toxicity caused by the past therapies; 9. patients who have history of drug abuse; 10. uncontrollable psychopaths； 11. uncontrollable diabetes； 12. pregnant or breast-feeding women, or patients(male and female) who have pregnancy plan; 13. patients who had received a therapy of another investigational drug within 12 weeks or patients who are still in another clinical trial at the enrollment; 14. known active hepatitis b/hepatitis c, positive hiv/ syphilis antibody; 15. patient who need long term treatment of cortical hormone or other immunosuppressive drugs such as visceral organ transplanters; 16. allergic to the investigational drug; 17. other patients judged ineligible for enrollment in the study by the investigator (sub-investigator). 18. patients who have received the therapy of adrenal steroid hormones within 1 week before enrollment or will receive the therapy for a long period time，except for corticosteroid nasal spray，inhaled steroid and topical steroids .